5-Methyl-1-phenyl-2-(1H)-pyridone (nonproprietary name: pirfenidone) is a medicine for pulmonary fibrosis as indication. Various effects of pirfenidone have been reported, for example, 1) treating effect for fibrosis in lung, arteriosclerotic lesion, or the like is described in JP Laid-Open (Tokukai) No. H02-215719, 2) a similar effect to 1) of pirfenidone analogs is described in JP Laid-Open (Tokuhyo) No. H08-510251, 3) usefulness for treating inflammation in respiratory organs or cutis is described in U.S. Pat. No. 3,974,281, U.S. Pat. No. 4,042,699, and U.S. Pat. No. 4,052,509, and 4) inhibiting effect to the synthesis and release of TNF-α is described in JP Laid-Open (Tokuhyo) No. H11-512699.
In the above-mentioned 1) and 2), exemplified as a dosage form of pirfenidone are capsule, tablet, powder, granule, syrup, injection, cream, ointment, insufflation, eye lotion, suppository, and pill, preferable is capsule, injection, cream, and ointment, and working examples are only capsule and ointment. A tablet of pirfenidone and its preparation are not described concretely.
With regard to the dosage of pirfenidone, 600 mg to 2400 mg is administrated three times a day in above-mentioned 1). In test example 1 of 2), capsule containing 800 mg, 1200 mg, and 1600 mg of pirfenidone are described. In order to obtain a sufficient therapeutic effect, pirfenidone must be administrated much higher dose in comparison with a usual medicine.
In general, there are eight types of capsule: No. 000, 00, 0, 1, 2, 3, 4, and 5. The bigger the number is, the smaller the size is. The general amount of a medicine contained in each capsule depending on the bulk density or compressibility of the medicine, as follows: about 60 mg to 100 mg in No. 5 capsule, about 100 mg to 170 mg in No. 4 capsule, about 140 mg to 220 mg in No. 3 capsule, about 180 mg to 300 mg in No. 2 capsule, about 240 mg to 390 mg in No. 1 capsule, and about 340 mg to 540 mg in No. 0 capsule. While No. 2 to No. 4 capsules have often been used for administration to human, a smaller types such as No. 3 to No. 5 capsules are becoming more popular in light of easy administration. A capsule usually contains not only an active ingredient, but also a pharmaceutical additive such as excipient, binder, and disintegrator, for improving the stability and efficacy of the active ingredient.
For example, if the amount of pirfenidone per one dose is 600 mg as mentioned above, amount of granules or mixed powder of pirfenidone to be filled in a capsule is about 800 mg to 850 mg. In encapsulating such an amount a No. 000 capsule or two No. 0 capsules are needed, and a patient has a strong pain during the administration. In case of much higher dose, it is impossible to prepare a practical capsule